U.S. patent application number 12/739337 was filed with the patent office on 2011-04-14 for cartridge for a biological sample.
Invention is credited to Vered Shany, Isaac Tavori.
Application Number | 20110086378 12/739337 |
Document ID | / |
Family ID | 40580176 |
Filed Date | 2011-04-14 |
United States Patent
Application |
20110086378 |
Kind Code |
A1 |
Shany; Vered ; et
al. |
April 14, 2011 |
Cartridge For a Biological Sample
Abstract
An assay device comprising a compartment adapted to receive a
sealed removable cartridge, wherein said cartridge is adapted to
contain a biologic sample and internally comprises two or more
assay locations, wherein said cartridge is adapted to facilitate
two or more assays of said biologic sample; and an actuator adapted
to interface with said cartridge to transport said biologic sample
towards at least one of said assay locations.
Inventors: |
Shany; Vered; (Ramat-Gan,
IL) ; Tavori; Isaac; (Ramat-Gan, IL) |
Family ID: |
40580176 |
Appl. No.: |
12/739337 |
Filed: |
October 23, 2008 |
PCT Filed: |
October 23, 2008 |
PCT NO: |
PCT/IB08/54381 |
371 Date: |
December 21, 2010 |
Current U.S.
Class: |
435/29 ;
435/287.1; 435/287.9; 435/288.7 |
Current CPC
Class: |
B01L 2400/0481 20130101;
B01L 2200/027 20130101; B01L 2300/0681 20130101; B01L 2400/0487
20130101; B01L 7/52 20130101; B01L 2300/0864 20130101; B01L
3/502753 20130101; B01L 3/502715 20130101; A61B 10/0045
20130101 |
Class at
Publication: |
435/29 ;
435/287.9; 435/287.1; 435/288.7 |
International
Class: |
C12Q 1/02 20060101
C12Q001/02; C12M 1/34 20060101 C12M001/34 |
Claims
1-46. (canceled)
47. A device for assaying at least one biological sample, wherein
said device comprising: a. at least one removable cartridge,
adapted to facilitate at least one assay of at least one of said
biologic sample, comprising a body; said body comprises: i. at
least one compartment adapted to contain said at least one biologic
sample; ii. at least one assay location, in which said assay of
said at least one biologic sample is enabled; and, b. at least one
actuator adapted to interface with said cartridge to enable
transportation of said biologic sample towards at least one of said
assay locations.
49. The device according to claim 47, wherein said removable
cartridge is sealed such that no contamination of the environment
outside said cartridge is enabled.
50. The device according to claim 47, additionally comprising a
reagent selected from a group consisting of cell support medium,
labeling compounds, markers, peptide, color-changeable pad or any
combination thereof; said reagent is adapted to, upon contact with
said biologic sample, to yield a reaction and/or a colored compound
indicating (i) existence; or, (ii) concentration of a component in
said sample; (iii) a result of said at least one assay.
51. The device according to claim 47, wherein said biologic sample
is selected from a group consisting of: a semen sample, a vaginal
secretion sample, a vaginal cell sample, a blood sample, a urine
sample, a saliva sample, a lymph sample or any combination
thereof.
52. The device according to claim 47, wherein said assay is
selected from a group consisting of: a sperm concentration assay, a
semen pH assay, a leukocyte threshold assay, a sperm motility
assay, a sperm morphology assay, a semen volume assay, a viscosity
assay and a turbidity assay; further wherein said assays is adapted
to facilitate diagnosis of at least one sexually transmitted
disease (STD) selected from a group consisting of: syphilis,
gonorrhea, Candida, human papilloma virus (HPV), mycoplasma,
ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes
simplex virus, Hepatitis B, Trichomonas and Hepatitis C.
53. The device according to claim 47, wherein said cartridge is
made of substantially rigid materials or a substantially flexible
materials or any combination thereof.
54. The device according to claim 47, wherein said actuator
comprises a pump, a peristaltic pump, means of pressure difference
creation, strike handle, a set of rollers, manual activation
selected from a pipette, micropipette injector, syringe, any
positive displacement or any combination thereof.
55. The device according to claim 47, further comprising a control
adapted to perform at least one action selected from a group
consisting of: (i) receive a reading from said at least one sensor,
said sensor is in communication with said cartridge; (ii) analyze
said reading; (iii) analysis readings received based upon said at
least one of said assays; and (iv) output said analysis of said
biological sample.
56. The device according to claim 47, wherein said cartridge is
further adapted to facilitate a cell separation assay; said cell
separation assay is adapted to assess motility of sperm cells
and/or isolate or separate motile sperm within a semen sample for
assisting fertility.
57. The device according to claim 47, wherein said assay is
performed in a cell separation system, said system comprising: a. a
first chamber adapted to contain at least a portion of said semen
sample; said first chamber is bounded by a rim, such that said
semen sample is kept below said rim; and, b. a second peripheral
chamber; said second peripheral chamber is characterized by
circumferential depression around said first chamber; said second
chamber is adapted to receive motile cells upon introduction of a
separation-enabling agent.
58. The device according to claim 57, wherein said rim is
configured with specific surface roughness or serration to
facilitate required surface tension capabilities for specific
sample/reagent combination.
59. The device according to claim 57, wherein said cell separation
system is adapted to isolate motile sperm cells of said semen
sample for a usage selected from a group consisting of: intra
uterine insemination (IUI), vaginal insemination, and in-vitro
fertilization (IVF) and diagnosis of motile sperm cell.
60. The device according to claim 59, wherein said
separation-enabling agent is selected from a group consisting of
Ringer's solution, Hartmann's solution, Saline, cell support
medium, cell washing medium, preparation medium or any
separation-enabling agent adapted to facilitate said separation of
said sperm cells from said semen sample.
61. The device according to claim 47, wherein said cartridge is
further adapted to manipulate said biologic sample using at least
one manipulation technique selected from a group consisting of:
homogenization, liquefaction, deposition on a reagent-loaded pad,
mixing with a reagent, deposition on an antibody-loaded pad,
incubation, separation, migration and sedimentation, and
swim-up.
62. The device according to claim 47, wherein said at least one
assay location comprises two or more assay locations.
63. A method for assaying at least one biological sample, said
method comprising steps of: a. providing a device; said device
comprises: i. at least one removable cartridge, said cartridge
comprising a body; said body comprises (a) at least one
compartment; and, (b) at least one assay location; ii. actuator
adapted to interface with said cartridge; b. operating said device
by steps of: i. inserting at least one biologic sample into said at
least one compartment within said body of said removable cartridge;
ii. operating said actuator, thereby transporting said at least one
biologic sample to at least one of said assay locations; iii.
activating said device, thereby facilitating at least one assay of
at least one of said biologic sample in said cartridge.
64. The method according to claim 63, additionally comprising a
step of providing said removable cartridge sealed such that no
contamination of the environment outside said cartridge is
enabled.
65. The method according to claim 63, additionally comprising a
step of contacting a reagent with said biologic sample, to yield a
reaction and/or a colored compound indicating (i) existence or (ii)
concentration of a component in said sample (iii) a result of said
at least one assay; further wherein said reagent is selected from a
group consisting of cell support medium, labeling compounds,
markers, peptide, color-changeable pad or any combination
thereof.
66. The method according to claim 63, wherein additionally
comprising at least one step selected from (i) selecting said
biologic sample from a group consisting of: a semen sample, a
vaginal secretion sample, a vaginal cell sample, a blood sample, a
urine sample, a saliva sample and a lymph sample or any combination
thereof; (b) selecting said assay from a group consisting of: a
sperm concentration assay, a semen pH assay, a leukocyte threshold
assay, a sperm motility assay, a sperm morphology assay and a semen
volume assay, a viscosity assay and a turbidity assay.
67. The method according to claim 63, additionally comprising step
of facilitating diagnosis of at least one sexually transmitted
disease (STD) selected from a group consisting of: syphilis,
gonorrhea, Candida, human papilloma virus (HPV), mycoplasma,
ureaplasma, human immunodeficiency virus (HIV), Chlamydia, herpes
simplex virus, Hepatitis B, Trichomonas and Hepatitis C by said
assay.
68. The method according to claim 63, additionally comprising a
step of selecting said actuator from a group consisting of a pump,
a peristaltic pump, means of pressure difference creation, strike
handle, a set of rollers, manual activation selected from a
pipette, micropipette injector, syringe, any positive displacement
or any combination thereof.
69. The method according to claim 63, further comprising at least
one step selected from a group consisting of: a. receiving a
reading from at least one sensor, said sensor is in communication
with said cartridge; b. analyzing said reading; c. analyzing
readings received based upon said at least one of said assays; and,
d. outputting said analysis of said biological sample via control
means.
70. The method according to claim 66, additionally comprising a
step of assessing motility of sperm cells and/or isolating motile
sperm within a semen sample for assisting fertility, by said cell
separation assay.
71. The method according to claim 63, additionally comprising a
step of manipulating said biologic sample using at least one
manipulation technique selected from a group consisting of:
homogenization, liquefaction, deposition on a reagent-loaded pad,
mixing with a reagent, deposition on an antibody-loaded pad,
incubation, separation, migration and sedimentation and swim up by
said cartridge.
72. The method according to claim 65, additionally comprising at
least one step selected from (a) providing said at least one assay
locations with two or more assay locations; or (b) providing said
at least one assay comprising two or more assays.
73. The method according to claim 65, additionally comprising step
of selecting said separation-enabling agent from a group consisting
of Ringer's solution, Hartmann's solution, Saline, cell support
medium, cell washing medium, preparation medium or any
separation-enabling agent adapted to facilitate said separation of
said sperm cells from said semen sample.
Description
FIELD OF THE DISCLOSURE
[0001] Embodiments of the disclosure relate to a biologic sample
assay device.
BACKGROUND
[0002] When diagnosing a sample, it is often required to reach a
significant conclusion with respect to the sample's contents.
Biological samples, such as semen, vaginal secretions, vaginal
cells, blood, urine, saliva, lymph and the like, are commonly
tested at the field, with portable apparatuses, tools or disposable
diagnostics, or in laboratories. Laboratory work, including field
work, often requires taking a portion of the sample, processing it
in various ways using laboratory operations and finally assessing a
result. Laboratory medicine commonly includes anatomic pathology
histopathology, cytopathology, microscopy, clinical microbiology,
bacteriology, virology, parasitology, immunology, mycology,
clinical biochemistry instrumental analysis, enzymology,
toxicology, endocrinology and hematology.
[0003] Over the past years, automated analyzers became more and
more common in laboratories. An automated analyzer is often defined
as a medical laboratory instrument designed to rapidly measure
different chemicals and other characteristics in a samples, with
minimal human assistance. The automation of laboratory testing does
not usually remove the need for human expertise (as some results
must still be evaluated by medical technologists and other
qualified clinical laboratory professionals, and sometimes manual
processing is required), but it does ease concerns about error
reduction, staffing concerns and safety.
[0004] Applicant's U.S. Provisional Patent Application No.
60/981,856, filed Oct. 23, 2007, discloses a diagnostic device.
This application is incorporated herein by reference in its
entirety.
SUMMARY
[0005] There is provided, according to an embodiment, an assay
device which includes a compartment adapted to receive a sealed
removable cartridge, wherein the cartridge is adapted to contain a
biologic sample and internally comprises two or more assay
locations, wherein the cartridge is adapted to facilitate two or
more assays of the biologic sample and an actuator adapted to
interface with the cartridge to transport the biologic sample
towards at least one of the assay locations.
[0006] According to further embodiments, the biologic sample may be
selected from a group that includes a semen sample, a vaginal
secretion sample, a vaginal cell sample, a blood sample, a urine
sample, a saliva sample, a lymph sample, or any combination
thereof.
[0007] According to additional embodiments, the two or more assays
may be selected from a group that includes a sperm concentration
assay, a semen pH assay, a leukocyte threshold assay, a sperm
motility assay, a sperm morphology assay, a semen volume assay, a
viscosity assay, a turbidity assay or any combination thereof.
According to yet further embodiments, at least one of the assays
may be adapted to facilitate diagnosis of at least one sexually
transmitted disease (STD) selected from a group that includes:
syphilis, gonorrhea, candida, human papilloma virus (HPV),
mycoplasma, ureaplasma, human immunodeficiency virus (HIV),
Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas and
Hepatitis C, or any combination thereof.
[0008] According to further embodiments, the housing of said
cartridge may be substantially rigid. The housing of the cartridge
may be substantially flexible.
[0009] According to yet additional embodiments, the assay device
may further include at least one sensor adapted to interface with
the cartridge to facilitate at least one assay of the assays. The
actuator of the assay device may include a pump.
[0010] According to additional embodiments, the assay device may
further include a computerized control adapted to perform at least
one action selected from a group consisting of: facilitate at least
one of the assays, receive a reading from the at least one sensor,
compute a result of at least one of the assays, compute a combined
measure of results of two or more of the assays and compute a
predicted optimal fertilization date.
[0011] According to further embodiments, the cartridge may further
include a cell separation system, which includes a first chamber
adapted to contain at least a portion of the semen sample; and a
second chamber adapted to receive motile cells upon introduction of
a separation-enabling agent into the first chamber. The cell
separation system may be adapted to assess motility of sperm cells.
The cell separation system may be adapted to isolate motile sperm
of said semen sample for a usage selected from a group consisting
of: intra uterine insemination (IUI), vaginal insemination, and
in-vitro fertilization (IVF).
[0012] According to yet further embodiments, the cartridge may be
further adapted to manipulate the biologic sample using at least
one manipulation technique selected from a group which includes
homogenization, liquefaction, deposition on a reagent-loaded pad,
mixing with a reagent, deposition on an antibody-loaded pad,
incubation, separation, migration, sedimentation, or any
combination thereof.
[0013] According to some embodiments there is provided a method for
operating an assay device, the method includes: inserting a sealed
removable cartridge into a compartment of the assay device;
inserting a biologic sample into the cartridge; and activating the
assay device to facilitate, within the cartridge, two or more
assays of the biologic sample.
[0014] According to further embodiments, the method for operating
an assay device may further include operating an actuator of the
assay device for interfacing with the cartridge and for
transporting the biologic sample towards at least two assay
locations where the two or more assays are facilitated.
[0015] According to yet further embodiments, the biologic sample in
the method for operating an assay device may be selected from a
group that includes a semen sample, a vaginal secretion sample, a
vaginal cell sample, a blood sample, a urine sample, a saliva
sample, a lymph sample, or any combination thereof.
[0016] According to additional embodiments, the two or more assays
in the method for operating an assay device may be selected from a
group that include a sperm concentration assay, a semen pH assay, a
leukocyte threshold assay, a sperm motility assay, a sperm
morphology assay, a semen volume assay, or any combination thereof.
According to additional embodiments, at least one of the assays is
adapted to facilitate diagnosis of at least one STD selected from a
group that includes syphilis, gonorrhea, candida, HPV, mycoplasma,
ureaplasma, HIV, Chlamydia, herpes simplex virus, Hepatitis B,
Trichomonas, Hepatitis C, or any combination thereof.
[0017] According to additional embodiments, the method for
operating an assay device may further include operating a
computerized control for performing at least one action selected
from a group consisting of: facilitate at least one of said assays,
receive a reading from said at least one sensor, compute a result
of at least one of said assays, compute a combined measure of
results of two or more of said assays and compute a predicted
optimal fertilization date.
[0018] According to yet further embodiments, the method for
operating an assay device may further include operating a cell
separation system of the cartridge, the operating includes:
depositing at least a portion of the semen sample in a first
chamber of the cell separation system; introducing a
separation-enabling agent into the first chamber, to facilitate
swimming of motile cell into a second chamber of the cell
separation system. The method may further include collecting the
motile cells from the second chamber. The collecting of the motile
cells may include collecting of motile sperm, for a usage selected
from a group that includes intra uterine insemination (IUI),
vaginal insemination, in-vitro fertilization (IVF), or any
combination thereof. The method may further include assessing
motility of cells based on a relative amount of motile cells in the
second chamber.
[0019] According to some embodiments, there is provided an assay
device which includes a compartment adapted to receive a receptacle
containing a reproductive system sample; one or more assay
locations adapted to facilitate at least one assay of said
reproductive system sample; and a result indicator adapted to
indicate a result of said at least one assay.
[0020] According to further embodiments, the reproductive system
sample includes a semen sample. The reproductive system sample
includes a vaginal secretion
[0021] According to additional embodiments, the assay device may
further include an extraction mechanism adapted to extract at least
a portion of the reproductive system sample from the receptacle.
The extraction mechanism may include a strike handle. The
extraction mechanism may include a peristaltic pump.
[0022] According to additional embodiments, the result indicator of
the assay device may include a color-changeable pad.
[0023] According to yet further embodiments, the receptacle may
include a condom.
[0024] According to additional embodiments, at least one of the
assay locations may include a replaceable assay location adapted to
be replaced by an additional assay location for facilitating an
additional assay. The one or more assay locations may include two
or more assay locations. The at least one assay may include two or
more assays. The at least one assay may be selected from a group
that includes a sperm concentration assay, a semen pH assay, a
leukocyte threshold assay, a sperm motility assay, a sperm
morphology assay, a semen volume assay, or any combination thereof.
The at least one assay may be adapted to facilitate diagnosis of at
least one STD selected from a group that includes syphilis,
gonorrhea, candida, HPV, mycoplasma, ureaplasma, HIV, Chlamydia,
herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C, or any
combination thereof.
[0025] According to further embodiments, the assay location may
further be adapted to manipulate the biologic sample using at least
one manipulation technique selected from a group that includes:
homogenization, liquefaction, deposition on a reagent-loaded pad,
mixing with a reagent, deposition on an antibody-loaded pad,
incubation, separation, migration, sedimentation, or any
combination thereof.
[0026] In some embodiments, the assay device may further include a
volume measurement chamber.
[0027] According to some embodiments there is provided a method for
operating an assay device, the method includes: inserting a
receptacle containing a reproductive system sample into a
compartment of the assay device; extracting at least a portion of
the reproductive system sample from the receptacle towards one or
more assay locations, to facilitate at least one assay of the
reproductive system sample; and reading at least one result of the
at least one assay from a result indicator of the assay device.
[0028] According to some embodiments, the reproductive system
sample may include a semen sample. The reproductive system sample
may include a vaginal secretion sample.
[0029] According to further embodiments, the method may further
include measuring a volume of the reproductive system sample.
[0030] According to additional embodiments, the biologic sample is
selected from a group that includes a semen sample, a vaginal
secretion sample, a vaginal cell sample, a blood sample, a urine
sample, a saliva sample, a lymph sample, or any combination
thereof.
[0031] According to yet further embodiments, the at least one assay
in the method may be selected from a group that includes a sperm
concentration assay, a semen pH assay, a leukocyte threshold assay,
a sperm motility assay, a sperm morphology assay, a semen volume
assay, or any combination thereof.
[0032] According to additional embodiments, the at least one assay
may be adapted to facilitate diagnosis of at least STD selected
from a group that includes: syphilis, gonorrhea, candida, HPV,
mycoplasma, ureaplasma, HIV, Chlamydia, herpes simplex virus,
Hepatitis B, Trichomonas, Hepatitis C, or any combination
thereof.
[0033] According to further embodiments the method may further
include replacing at least one of the assay locations with an
additional assay location.
[0034] In addition to the exemplary aspects and embodiments
described above, further aspects and embodiments will become
apparent by reference to the figures and by study of the following
detailed description.
BRIEF DESCRIPTION OF THE FIGURES
[0035] Exemplary embodiments are illustrated in referenced figures.
Dimensions of components and features shown in the figures are
generally chosen for convenience and clarity of presentation and
are not necessarily shown to scale. It is intended that the
embodiments and figures disclosed herein are to be considered
illustrative rather than restrictive. The figures are listed
below.
[0036] FIG. 1A shows an exploded view of a sealed, removable
cartridge;
[0037] FIG. 1B shows a perspective view of a main body of a sealed,
removable cartridge;
[0038] FIG. 1C shows a perspective view of another sealed,
removable cartridge;
[0039] FIG. 2 shows an exploded view of an assay device;
[0040] FIG. 3A shows a cross-sectional view of a cell separation
system;
[0041] FIG. 3B shows a top view of a cell separation system;
[0042] FIG. 4A shows a perspective view of an assay device;
[0043] FIG. 4B shows a perspective view of a receptacle; and
[0044] FIG. 4C shows a cross-sectional view of an assay device.
DETAILED DESCRIPTION
[0045] An aspect of some embodiments related to an assay device
adapted to receive a sealed, removable cartridge containing a
biologic sample. The assay device, in conjunction with the
cartridge, may be used for assessing, by way of at least one assay,
one or more parameters pertaining to the biologic sample.
Additionally or alternatively, the assay device may be used for
treating the biologic sample, such as, in the case of a semen
sample, preparing it for intra uterine insemination (IUI), vaginal
insemination, and/or in-vitro fertilization (IVF).
[0046] The biologic sample may be, for example, a semen sample, a
vaginal secretion sample, a biologic cell sample, cervical mucus, a
blood sample, a urine sample, a saliva sample, a lymph sample, or
any other sample of biologic matter collected from a human or any
other animal.
[0047] The cartridge may be substantially sealed, so that its
biologic contents do not come in direct contact with the assay
device and therefore no substantial contamination of the assay
device and/or its immediate surroundings is caused. The sealed
cartridge may, however, include an input port through which the
biologic sample is fed, and/or an exhaust for discarding excess
pressure--but both features may be configured in such a way that no
substantial contamination is caused
[0048] The assay device may interface with the cartridge using an
actuator adapted to transport the biologic sample within the
cartridge, towards one or more locations within the cartridge
referred to as assay port(s) and/or treatment port(s), where the
biologic sample is assessed and/or treated, respectively.
[0049] After use, the cartridge may be removed from the assay
device and discarded. Alternatively, the cartridge may be stored
(such as in cooled or cryogenic storage), along with its contents,
for future testing, analysis and/or treatment of the sample. The
cartridge may be configured such that only a part of it, containing
portion of sample or the treated sample, is removed and stored for
further testing, analysis and/or treatment.
[0050] The assay device may be relatively easy to operate and its
operation may require no special laboratory training, so that a
nurse, a physician, or any other caregiver may operates it in what
is often referred to as a "point of care--a clinic, a medical
institution or the like. Furthermore, the assay device may still be
operated at the field, such as with portable apparatuses, tools or
disposable diagnostics or in a laboratory.
[0051] Another aspect of some embodiments relates to an assay
device adapted to receive a receptacle, such as a condom or any
sample collection cup, containing a reproductive system sample such
as semen, a vaginal secretion, any type of cell found in the
vagina, cervical mucus and/or the like. In case the sample is
semen, the assay device may be used for assessing, using at least
one assay, one or more parameters pertaining to the semen sample
and/or for treating the sperm sample.
[0052] The assay device may include an extraction mechanism for
extracting the semen sample from the receptacle and for
transporting the semen sample towards one or more assay locations
where the semen sample is assessed.
[0053] The assay device may further include a result indicator,
such as a color-changeable pad, for conveying the assessment
results to its user.
[0054] Optionally, the user is the reproductive system sample
provider, and, accordingly, the assay device may be adapted for use
by a non-medically trained person. The assay device may be
therefore offered to consumers either as a prescription medical
device or as an over-the-counter (OTC) non-prescription device.
[0055] An additional aspect of some embodiments relates to the
sealed, removable cartridge itself, which may be adapted for use in
conjunction with an assay device or as a standalone solution.
[0056] The cartridge may be essentially rigid or essentially
flexible, and may include an actuator interface for interfacing
with an external means of pressure creation, so as to transport the
biologic sample towards one or more assay and/or treatment ports.
In case the cartridge is used with the assay device, the means of
pressure difference creation may be a part of the assay device.
Additionally or alternatively, the actuator may be an essentially
flexible area of the cartridge, which may be pressed, optionally
manually, to transport the sample.
[0057] A further aspect of some embodiments relates to a cell
separation system. When used with sperm cells, it is adapted to
assess motility of sperm cells and/or to isolate motile sperm cells
of the semen sample for intra uterine insemination (IUI), vaginal
insemination, or in-vitro fertilization (IVF) purposes. The cell
separation system may also be used for separating other types of
motile cells from immotile cells.
[0058] The cell separation system may include a first chamber
adapted to contain at least a portion of a semen sample, and a
second chamber adapted to receive motile cells upon introduction of
a separation-enabling agent into the first chamber. The
separation-enabling agent may be a gas, a liquid, a gel and/or any
other suitable substance. After the separation, the first chamber
may include an enriched population of immotile cells while the
second chamber may include an enriched population of motile
cells.
[0059] The cell separation system is optionally enclosed within the
cartridge which is, in turn, adapted for insertion into the assay
device. Alternatively, the cell separation system may be used as a
standalone device, separate from the cartridge and assay device
discussed above.
A Cartridge
[0060] Reference is now made to FIG. 1A, which shows an exploded
view of an exemplary sealed, removable cartridge 100 (hereinafter
"cartridge"), in accordance with an embodiment. Cartridge 100 may
include a main body 102, a top cover 104 and optionally a base 106.
Main body 102 is also shown, from a perspective view, in FIG. 1B.
Main body 102 may be shaped as a rectangular box, a cylinder a
flexible pouch and/or the like.
[0061] At least one of main body 102, top cover 104 and base 106
(the at least one of them may be jointly referred to as a
"housing") may be essentially rigid, optionally made of a rigid
material such as a polymer, a metal, glass or the like;
alternatively, the at least one of main body 102, top cover 104
and/or base 106 may be made of a combination of rigid materials or
of a combination of at least one rigid material and at least one
flexible material.
[0062] Main body 102 may include an inlet 108a for insertion of a
biologic sample into cartridge 100. A matching hole 108b may exist
in top cover 104, to allow for a connection of a sample cup (not
shown) to cartridge 100. The sample cup may have a tip adapted to
be inserted, at least partially, into hole 108b and into inlet
108a, for supplying the biologic sample, while maintaining overall
sealing as discussed above.
[0063] The inserted biologic sample may be transported inside
cartridge 100 by virtue of at least one vacuum conduit, such as
conduits 110. Conduits 110 may include internal tubing not visible
in this figure. Conduits 110, when containing fluid, may be in
contact with at least one actuator interface, such as actuator
interfaces 112a-b. Actuator interfaces 112a-b may be shaped as a
niche (optionally arched) in main body 102.
[0064] At least one external actuator (not shown) interfacing with
actuator interfaces 112a-b, may provide conduits 110 with positive
or negative gas pressure, so that the biologic sample is pushed or
pulled along the conduits. For example, the actuator may be a
peristaltic pump adapted to apply peristaltic pressure on a
flexible pipe 114 which is in fluid contact with conduits 110.
Flexible pipe 114 may be secured in place using, for example, two
holders 116. Since there is optionally no fluid contact with the
outside environment, by virtue of the peristaltic pump which
operates externally on flexible pipe 114, the interfacing with the
actuator does not cause contamination of the environment outside
cartridge 100. For this purpose, any positive displacement system
such as a syringe or a micropipette may be used. In some cases,
electromagnetic fields may induce transportation of the sample or
part of the sample using, for example, electrophoresis. In some
cases, an electron enriched material such as a salt gradient may be
used.
[0065] Alternatively or additionally, another actuator interface
(not shown) may be an essentially flexible portion of cartridge 100
and/or its internal tubes, adapted for manual squeezing in order to
transport the biologic sample.
[0066] A set of filters 118 may be positioned in between the edge
of conduits 110 and an elevation 120 of base 106. Similarly, a
filter 122 may be positioned in between a volume compartment 124
and another elevation 126 of base 106. Filters 122 and 118 may, by
virtue of a suitably small pore size, provide ventilation to
cartridge 100, while preventing leakage of hazardous materials to
the environment.
[0067] Cartridge 100 may include two or more assay locations
adapted to facilitate, within the cartridge, two or more assays of
the biologic sample. The term "assay location", as referred to
herein, may refer to any site within cartridge 100 adapted to act
on the biologic sample and/or to analyze (or enable analysis by an
external sensor of an assay device) at least one parameter
pertaining to the sample.
[0068] For example, optionally when the sample is semen, the two or
more assay locations may be selected from the following: at least
one result pad such as two result pads 128; at least one pH and/or
leukocytes test 132; at least one morphology assay 134; at least
one reagent location, such as five reagent locations 136; at least
one homogenizer, such as two homogenizers 138; at least one cell
separation system 140; and at least one free volume compartment
124.
[0069] The assay location may be adapted to perform assays such as:
Acrosom reaction assay, with or without calcium ionophore; a 23187
ARIC test and progesterone; bio active recombinant human ZP3 or
active synthetic ZP3 peptides or analogues; adding reagent (for
example 7-amino-actinomycin-D) to identify necrotic cells (SYTO 16)
and reading results at 610 nm to 670 nm hence detecting apoptosis;
Sanger sequencing; microplate assay; Polymerase Chain Reaction
(PCR); probe-based hybridization assay; Processor Aided Motility
count (CASA); Peroxidase; Zinc at 560 nm; Fructose at 470 nm;
glucosidase at 405 nm; heavy metals assay; hormones such as
Progesterone, Testosterone, and Estrogen; Antigen and/or cancer
markers such as PSA, trace elements, carbohydrates proteoglycans or
glycoproteins, minerals blood cells, plasma sexually transmitted
disease (STD) assay (such as bacteria; yeast; Candida; virus)
germs; Hidukes; Cervix carcinoma assay; PAP smear, blood assay;
saliva assay; urine stick assay; Immunobead assay; mixed
antiglobuline reaction test (MAR test) assay; induced acrosom
reaction assay; measurement of reacting oxygen assay; ROS-Oxidative
stress, anti oxidants, sperm-cervical mucus interaction assay,
turbidity, viscosity and/or the like in ways known in the prior
art.
[0070] The assay location may perform its assay at least partially
by manipulating the biologic sample. By way of example, the assay
location may utilize one or more of the following sample
manipulation techniques: homogenization, liquefaction, mixing with
a reagent, mixing with an antibody, deposition on a reagent-loaded
pad, deposition on an antibody-loaded pad, concentration
assessment, incubation, separation, migration, sedimentation
viscosity assessment, turbidity, and the like.
[0071] The assay may be adapted to facilitate diagnosis of at least
one STD. For example, syphilis, gonorrhea, candida, human papilloma
virus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus
(HIV), Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas,
Hepatitis C and/or any other STD or infection.
[0072] The assay may further be adapted to facilitate diagnosis of
one or more fertility factors or indicators of the tested subject,
such as sperm cell concentration, semen volume, sperm cell
morphology, semen pH, female secretion, sperm-cervical mucus
interaction and/or the like
[0073] Result pads 128 may be loaded with a reagent, and when
sample is delivered via tips 130, reaction occurs and a result is
shown (also referred to as classical flow-through diagnostics).
Result pad 128 may be used as a strainer of the sample if reaction
with reagents is performed within the homogenizer, as described
below. Result pad 128 may be coupled with an antibody agent. When
the sample is delivered via tips 130, it flows on or within result
pads 128 until in reaction with an antibody compound (also referred
to as classical lateral flow diagnostics). For example, anti CD 59
Result pad 128 may be operable for adding a reagent to the sample
already on the result pad, using a gas and/or a liquid. The gas
and/or the liquid may flow onto the sample through tips 130.
Results may be read visually as color, a texture, a shape and/or
the like. Results may also be read by a sensor.
[0074] Homogenizers 138 may be operable for homogenizing the sample
prior to performing further assays and/or for mixing the sample
with other reagents and/or biological components. Homogenization
may be achieved via rapid movement of the sample, such as by mixing
it using a rotateable or a reciprocating member. For example,
triangular mixers 138a may be used for mixing the sample.
[0075] Semen pH threshold and leukocytes threshold tests 132 may
include an absorbent pad holder 132a. The pad may include a
color-changeable reagent indicating pH level, and/or a
color-changeable reagent indicating leukocyte level. Such pads are
available from different manufacturers.
[0076] Sperm cell morphology assay 134, which is shown only
schematically since it is located within main body 102, may be
adapted to hold, mark, stain and/or analyze morphological
characteristics of the biologic sample. For example, if the
biologic sample is semen, morphology assay 134 may analyze
morphological defects of the sperm cells which may degrade its
fertilization potential. Sperm cells morphology assay 134 may be
detached from cartridge 100 and held for further diagnosis.
[0077] Reagent locations 136 may each include a reagent container.
The reagent, upon contact with the biologic sample, may yield a
reaction and/or a colored compound indicating existence and/or
concentration of a component in the sample. Other reagents such as
cell support medium, labeling compounds, markers, peptide and the
like, available from various companies, may also be used.
[0078] Cell separation system 140 may be adapted to assess motility
of sperm cells or any other cells of the biologic sample.
Additionally or alternatively, cell separation system 140 may be
adapted to isolate motile sperm cells of the semen sample for intra
uterine insemination (IUI), vaginal insemination, and/or in-vitro
fertilization (IVF) purposes.
[0079] Cell separation system 140 may be based upon the principle
that motile cells (such as, for example, sperm cells) have swimming
abilities, whereas immotile cells lack these abilities, at least to
some extent. Therefore, cell separation system 140 is constructed
such that motile cells move, essentially using their own swimming
capabilities, to a different location, while a sediment of immotile
cells is left behind.
[0080] Reference is now made to FIGS. 3A and 3B, which show cell
separation system 140 in more detail. FIG. 3A is a cross-sectional
view and FIG. 3B is a top view. Cells separation system 140 may
include two chambers: a central chamber 302 shaped as a dimple in
main body 102, and a peripheral chamber 304 shaped as a shallower,
circumferential depression around the central chamber.
[0081] In order to operate cell separation system 140, a biologic
sample (such as semen) 308 is deposited inside central chamber 302,
while keeping the sample's level below a rim 306. Rim 306, may be
dimensioned and designed with specific surface roughness or
serration in order to facilitate required surface tension
capabilities for specific sample/reagent combination. A
separation-enabling agent 310, such as a Ringer's solution,
Hartmann's solution, Saline and/or the like is then introduced into
central chamber 302 and/or into peripheral chamber 304, such that
the separation-enabling agent covers both the entirety of central
chamber 302 and at least a portion of peripheral chamber 304.
[0082] Then, semen sample 308 and separation-enabling agent 310 may
be left for a period of optionally 15 to 60 minutes in a
temperature of optionally 30-37 degrees Celsius, allowing motile
cells to swim up through separation-enabling agent 310 and at least
partially into peripheral chamber 304. After the specified period,
the motile cells may be collected, manually or automatically, from
peripheral chamber 304.
[0083] Cell separation system 140 may also be operated inversely--a
sample may be deposited in peripheral chamber 304 keeping its level
below rim 306; a separation-enabling agent may be introduced into
central chamber 302 while overflowing rim 306 onto the peripheral
chamber; and the components may be left to allow motile cells to
swim up from the peripheral chamber into the central chamber.
[0084] Generally, a cell separation system such as system 140 or
any other system may be constructed according to the principle that
a first chamber is adapted to contain a semen sample, and a second
chamber is adapted to receive motile cells upon introduction of a
separation-enabling agent into the first chamber. In the examples
given above, respectively, each of central chamber 302 and
peripheral chamber 304 may be the first or the second chamber.
[0085] Cell separation system 140 may be used to assess motility of
sperm cells of the semen sample, and/or to isolate motile sperm
cells of the semen sample for intra uterine insemination (IUI),
vaginal insemination and/or in-vitro fertilization (IVF)
purposes.
[0086] Referring now back to FIGS. 1A and 1B, free volume
compartment 124 may be adapted to measure and/or to dose the volume
or a portion of the volume of the biologic sample. Free volume
compartment 124 may be used to hold required dose of the sample and
than transfer it to the correct assay, as different assays require
different volumes of sample. The volume may be manually read, such
as by reading the scale at the sample surface level or by a sensor
adapted for such reading.
[0087] Reference is now made to FIG. 1C, which shows a perspective
view of another exemplary sealed, removable cartridge 170,
according to an embodiment. Cartridge 170 may differ from cartridge
100 (FIGS. 1A-B), inter alia, in its essentially flexible housing
172. Flexible housing 172 may be made of any flexible material,
such as a polymer, an IV pouch, a food/liquid storage pouch, a
hazardous material storage pouch, or any other pouch. Internal
conduits 176 may also be flexible, to enable manual or automatic
squeezing of housing 172 and the conduits to transport a biologic
sample within cartridge 170, towards two or more assay locations
such as assay locations 178 and 180.
An Assay Device
[0088] Reference is now made to FIG. 2, which shows an exploded
view of an exemplary assay device 200, according to an embodiment.
Assay device 200 may include a compartment 202 or any other cavity
adapted to receive a cartridge 204, which may be cartridge 100 of
FIGS. 1A-B, cartridge 170 of FIG. 1C or any other suitable
cartridge. Compartment 202 is shown, for simplicity of
presentation, as a space above a base 206 of assay device 200. In
other embodiments (not shown), a compartment may be a slot, a
recess and/or any other cavity adapted for partial or full
insertion of a cartridge.
[0089] Assay device 200 may further include a top cover 208 having
a handle 210. Top cover 208 may be pivotally connected to base 206,
to enable opening of the top cover for insertion and removal of
cartridge 204. In other embodiments (not shown), an assay device
may structured such that insertion and removal of a cartridge do
not necessitate manual opening of a cover, a door or the like. For
example, an assay device may include an automatically-opening door
or a door which opens upon physical engagement of a cartridge.
Alternatively, an assay device may lack a cover or a door at all,
so that at least a portion of a cartridge remains exposed when the
cartridge is inside its compartment.
[0090] Assay device 200 may further include an actuator 212 adapted
to interface with cartridge 204 and to provide positive and/or
negative gas (such as air or any other suitable gas) pressure to
the cartridge. The pressure created by actuator 212 may propagate
along one or more conduits within cartridge 204, so that a biologic
sample contained in the cartridge is transported along the
cartridge. Actuator 212 may be a pump, such as a positive
displacement pump, a peristaltic pump or any other type of pump
adapted to provide positive and/or negative pressure to the one or
more conduits of cartridge 204. Additionally or alternatively, a
common syringe or a micropipette, manually or machine operated, may
be used.
[0091] Additionally or alternatively, a different actuator (not
shown) may be at least one roller adapted to squeeze cartridge 204
(or a different cartridge) in order to transport the biologic
sample within it.
[0092] Assay device 200 may include a means for reading results, or
to inspect any other assay within cartridge 100. Results may be
read visually, or the device may further include one or more
sensors, such as, for example, three sensors 214. At least one of
sensors 214 may be adapted to sense one or more parameters
pertaining to the biologic sample in cartridge 204, and may be
positioned such that it is in sensing stance of at least one assay
location of the cartridge.
[0093] For example, at least one of sensors 214 may be an image
sensor, namely--a camera, adapted to visually inspect at least one
assay location of cartridge 204. The image sensor may sense, for
instance, a color (via sensed wavelength), a texture and/or the
like which exist in the at least one assay ports. The color (via
sensed wavelength), a texture and/or shape may be indicative of one
or more parameters of the biologic sample. For example, the image
sensor may be adapted to sense light at 610-670 nanometers (nm) for
detecting apoptosis in the biologic sample. As another example, pH
may be read by pH electrode; Turbidity and viscosity sensors may be
ones available on the market; a pad loaded with specific reagents
also available on the market.
[0094] Assay device 200 may further include a processor 216,
adapted to control at least one of sensors 214 and/or to process
data received from the sensors. Processor 216 may be realized as
any available micro processor, micro controller and/or general
purpose computer. For example, processor 216 may display locally to
its user results of one or more assays performed in cartridge 204.
The results may be stored for further processing, displayed in a
remote location and/or transferred using communication protocols
known in the industry, wired or wireless. As another example, if
the biologic sample is a semen sample, processor 216 may analyze a
series of temporally-distinct semen samples of the same person, and
provide the user with a prediction of an optimal date in which the
person's semen may be best for fertilization. That is, processor
216 may recognize a pattern of gradually changing fertility factors
(such as sperm cell concentration, sperm cell motility and/or the
like) and calculate, accordingly, future fertility factors in that
same tested person. When conducting an assay of female factors, for
example, estrogen and progesterone profiles, it may be possible to
predict a date in which fertilization is in its best. Combining
both predictions yields a better chance for successful
fertilization, and an "optimal fertilization date" may be jointly
determined.
[0095] Processor 216 may be further adapted to perform one or more
of facilitating at least one of the assays, receiving a reading
from the at least one sensor, computing a result of at least one of
the assays, and/or computing a combined measure of results of two
or more of the assays, hence concluding different results. Such a
combined measure may be used as a fertility index. As an example,
male subjects with low sperm qualities may get a higher index score
by changing their way of life, avoiding oxidative stress or other
methods known in prior art.
[0096] Reference is now made to FIG. 4, which shows a perspective
view of another assay device 400, according to an embodiment. Assay
device 400 may be relatively easy to operate and its operation may
require no special laboratory training, so that a nurse, a
physician, or any other caregiver may operate it in what is often
referred to as a "point of care"--a clinic, a medical institution
or the like. Furthermore, the assay device may still be operated in
a laboratory.
[0097] Assay device 400 may include a compartment 402 adapted to
receive a receptacle, such as a condom or a sample collecting cup,
containing a reproduction system sample such as semen, vaginal
secretions, cervical mucus, vaginally-collected cells and/or the
like. Optionally, the receptacle is the one disclosed in
applicant's PCT Published Application No. WO 2008/035333.
[0098] Referring now to FIG. 4B, an exemplary receptacle 440 is
shown. Receptacle 440 may include an elongated, flexible bag, which
may have a condom-like shape with inner cavity (such as 443)
defined by the walls of the receptacle bag (440). The narrow end
442A of the receptacle may be at least partially sealed. For
example, the walls at the narrow end of the receptacle may exhibit
pore sizes of less then 0.42 nm. The broad end 442B, which is
distally opposing the narrow end 442A, may be open. The broad, open
end 442B may further include a rim 444 that may be used for the
association of the receptacle within a contraceptive, as detailed
below herein. Rim 444 is illustrated at a deformed state, wherein
the rim is shaped into an eight form, by, for example, pinching two
opposing sides of the rim towards each other. The receptacle 440
may be constructed of rubber, silk, polyurethane, silicone and the
like. The thickness of the receptacle may vary in the range of
about 5 to 1500 microns. Size of receptacle 140 may vary in length
and diameter. For example, length of receptacle 440 from end 442A
to end 442B may be in the range of, about 100-200 mm. For example,
diameter of rim 444 of receptacle 440 may be in the range of, about
37 to 60 millimeter. Receptacle (such as 440) may further be
associated with a male contraceptive device, such as a condom 446.
Receptacle 440 may be fitted into male condom 446, such that the
receptacle is contained within the inner space of the condom. Shown
in FIG. 4B is a receptacle 440 fitted about two thirds of its
length into a condom 446. Receptacle 440 may be secured to condom
446 by various ways. For example, rim 444 and rim 448 of condom 446
may be associated by pressing, stitching, mechanical fitting,
zip-lock fit, zipper fit, fitting grooves, adhering, gluing and the
like. For example, rim 444 of receptacle 440 may include
perforation/grooves that may be used to fit to the upper rim, 448
of condom 446.
[0099] Reference is now made back to FIG. 4A. Assay device 400 may
include an extraction mechanism for extracting the reproduction
system sample from the receptacle and for transporting the
reproduction system sample towards one or more assay ports and/or
treatment ports, where the reproduction system sample is assessed
and/or treated, respectively.
[0100] The extraction mechanism may be embodied as a strike handle
404 pivotally attached to a main body 410 of assay device 400, and
having a protruding structure 406 matching a structure of a recess
408 in the main body. The receptacle may be positioned in
compartment 402 with its reproduction system sample-containing edge
at recess 408, and handle 404 may be lowered so as to squeeze the
receptacle and extract at least some of its reproduction system
contents.
[0101] Alternatively, the extraction mechanism may include a
peristaltic pump (not shown) and/or a set of rollers adapted to
induce the reproduction system sample out of the receptacle.
Alternatively, the extraction mechanism may be the receptacle
itself, being elastic in nature and therefore manually squeezable
by a user.
[0102] Reference is now made to FIG. 4C, which shows a
cross-sectional view of assay device 400. Before, during or after
extraction of the receptacle's reproduction system contents, the
volume of the reproduction system is optionally measured in a
chamber 412.
[0103] The extracted reproduction system may be forced, by virtue
of the extraction mechanism, to a conduit 414 leading to one or
more assay locations, such as assay location 416. The one or more
assays are optionally those described above in regard to cartridge
100 (FIGS. 1A-B).
[0104] When the one or more assays are complete, at least one
chemical may flow to a result indicator such as a color-changeable
result pad 418, causing the pad to change color responsive to the
assay result. Result pad 418 may be embedded in a sliding base 420
of assay device, and the sliding base may be pivotally attached,
using a hinge 422, to main body 410. Sliding base 420 may be slid
by the user when the one or more assays are complete, to reveal
result pad 418 and see the result.
[0105] Handle 404, or any other part of assay device 400, may
include a reference color scale (not shown) for comparing the
shade, shape, texture and/or the like of result pad 418 to a
reference and thus providing the user with a meaningful result. The
reference color scale may be printed on handle 404 or attached to
it as a sticker. The reference color scale optionally includes
literal explanation of the meaning of each color; the explanation
may, additionally or alternatively, be included in product
literature accompanying assay device 400.
[0106] Optionally, assay location 416 is a replaceable, and is
adapted to be replaced by an additional assay location for
facilitating an additional assay. This way, assay device 400 may be
used multiple types for performing the same assay (such as an assay
pertaining to fertilization potential which may have to be repeated
every once in a while) or may be used each time for performing a
different assay of the same semen sample or a different semen
sample.
[0107] While a number of exemplary aspects and embodiments have
been discussed above, those of skill in the art will recognize
certain modifications, permutations, additions and sub-combinations
thereof. It is therefore intended that the following appended
claims and claims hereafter introduced be interpreted to include
all such modifications, permutations, additions and
sub-combinations as are within their true spirit and scope.
[0108] In the description and claims of the application, each of
the words "comprise" "include" and "have", and forms thereof, are
not necessarily limited to members in a list with which the words
may be associated.
* * * * *